Changes

==Primary Author(s)*==

==Primary Author(s)*==

Beth Pitel, MS, ASCP(CG)CM

Beth Pitel, MS, ASCP(CG)CM

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The ''TP53'' gene contains homozygous mutations in about 50-60% of human cancers. About 90% of the mutations in ''TP53'' encode missense mutant proteins that span about 190 codons in the DNA-binding domain; none of the 50 most common pathogenic missense mutations occur outside of the DNA-binding region. These mutations produce a protein with a reduced capacity to bind to a specific DNA sequence that regulates p53 transcriptional pathway [15]. The eight most common mutations across all cancer types (R175H, R248Q, R273H, R248W, R273C, R282W, G245S, R249S) are found in codons that account for about 28% of the total p53 mutations (See Table 1 in [15]); these alleles appear to be selected for preferentially in human cancers of many tissue types. Seven of the eight mutations occur at methylated CpG sites in ''TP53'', which encode arginine residues that contact the DNA and are conserved over evolutionary time scales [15].

The ''TP53'' gene contains homozygous mutations in about 50-60% of human cancers. About 90% of the mutations in ''TP53'' encode missense mutant proteins that span about 190 codons in the DNA-binding domain; none of the 50 most common pathogenic missense mutations occur outside of the DNA-binding region. These mutations produce a protein with a reduced capacity to bind to a specific DNA sequence that regulates p53 transcriptional pathway [15]. The eight most common mutations across all cancer types (R175H, R248Q, R273H, R248W, R273C, R282W, G245S, R249S) are found in codons that account for about 28% of the total p53 mutations (See Table 1 in [15]); these alleles appear to be selected for preferentially in human cancers of many tissue types. Seven of the eight mutations occur at methylated CpG sites in ''TP53'', which encode arginine residues that contact the DNA and are conserved over evolutionary time scales [15].

Inactivating mutations resulting in loss of p53 function, including deletions, LOH, and loss of function (LOF) alterations often confer a poor prognosis and chemoresistance.  Alternatively, gain-of-function mutations promoting the expression and stability of the p53 protein in the nucleus can also lead to oncogenic effects, including genomic instability and excessive cell proliferation [12].

Inactivating mutations resulting in loss of p53 function, including deletions, LOH, and loss of function (LOF) alterations often confer a poor prognosis and chemoresistance.  Alternatively, gain-of-function mutations promoting the expression and stability of the p53 protein in the nucleus can also lead to oncogenic effects, including genomic instability and excessive cell proliferation [12].

{| class="wikitable sortable"

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! Copy Number Loss   !! Copy Number Gain   !! LOH   !!   Loss-of-Function Mutation   !! Gain-of-Function Mutation !! Translocation/Fusion  

!Copy Number Loss!!Copy Number Gain!!LOH!!Loss-of-Function Mutation!!Gain-of-Function Mutation!!Translocation/Fusion

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| X || || X || X || X ||

|X|| ||X||X||X||

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17. Kato S, et al., (2003). Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci USA 100(14):8424-8429, PMID 12826609.

17. Kato S, et al., (2003). Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci USA 100(14):8424-8429, PMID 12826609.

== Notes ==

==Notes==

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

[[Category:Cancer Genes T]]

[[Category:Cancer Genes T]]

[[Category:Tumor Suppressor Genes T]]

[[Category:Tumor Suppressor Genes T]]

[[Category:Oncogenes T]]

[[Category:Oncogenes T]]